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Here we review modern data on appearance and maintenance of depression at different levels of the body. We discuss a role of impairments of emotional and motivation mechanisms of adaptive behavior in genesis of depression. We demonstate an interaction of stress response and neuroinflammatory processes in pathogenesis of depression and analyze the effects of these molecular cascades on neurotrophic support of the central mechanisms of memory and neurogenesis.

In this review the data on consolidation and reconsolidation of memory by its reactivation (reminding) by a conditional stimulus or context are presented. A special attention is paid to "time windows" when amnesic and other interventions during memory reconsolidation become effective. The similarities and differences between consolidation of original learning and repeated consolidation (reconsolidation) during reactivation of memory by a conditional stimulus or context are considered. The hypotheses about memory updating during reconsolidation and some possible ways affecting memory are also discussed.

A review. Current models of aggressive behavior in animals are described. They include aggression due to social isolation; territorial aggression in pair "intruder-resident"; aggression elicited by direct electrical stimulation of the brain; maternal aggression; learned aggression and genetic models. The models are analyzed comparatively and their application to human aggression is discussed. Effects of different compounds on aggression are considered and involvement of some neurotransmitters and hormones in aggressive behavior is discussed.

In the current paper a role of the serotinergic system in organization of impulsive behaviour in animals was considered. The results of influence of antagonists and agonists of the different types and subtypes of 5-HT receptors (1A, B; 2A, B, C; 7) and the effects of the dorsal raphe nuclei lesions on characteristics of impulsivity related with a motor control, mechanisms of attention, reinforcement and decision making were summarized. The data on knock-out animals and the experiments with microdialysis have been also considered. There was emphasized the important role of interaction of 5-HT-, dopamine- and glutamatergic systems in mediation of impulsive behaviour.

In this paper a structure of a microdialytic cannula inserted into brain areas just before a microdialysis is described. The cannula used allowed to find out a correspondence of behavioral and biochemical changes in C57BL/6 mice at various time intervals after a single dose administration (20 mg/kg) of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, without any additional pharmacological actions enhancing an extracellular striatal dopamine concentration. Immediately after 1-methyl-4-phenyl-1.2,3.6-tetrahydropyridine administration an essential disturbance of mice behavior and a significant reduction of the extracellular concentration of dopamine and homovanillic acid were observed in striatum. A week after the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration neither behavior nor the extracellular dopamine and homovanillic acid striatal concentration substantially differed from those of controls. 30 days after the neurotoxin administration there was again an essential disturbance of behavior and the large reduction of dopamine and its metabolite concentration in striatum. There was suggested that a reduction of the dopamine concentration immediately after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection connected with abnormalities of dopamine synthesis and metabolism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine whereas a reduction of the extracellular striatal dopamine concentration 30 days after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration related to damage of the nigrastriatal dopaminergic system.

The influence of enriched environment on the long-term posttetanic potentiation of hippocampal evoked potentials is discussed. The attention is focused on the effects of novelty, aging and the influence of enriched environment on synaptic processes in hippocampal neurons in transgenic animals. The evidence that the exposure to the enrichment of the environments prevents the negative effects of stress and other unfavorable factors on the long-term posttetanic potentiation, learning and memory is presented. The molecular-biochemical, neurochemical, neurophysiological and morphological mechanisms underling synaptic changes responsible for the transformation of hippocampal long-term potentiation under exposure to the enriched environment are considered.

Different types of individual behavior are described in terms of under- or overestimation of reinforcement characteristics by the brain under conditions of uncertainty of reinforcement presentation. The following important biological characteristics of a subject are discussed, such as anxiety, fear, neuroticism, impulsiveness, self-control and psychoticism that determine the main individual-typological features in human and animals. Some modern biological theories of "individuality" and recent animal studies of neuronal activity of the frontal cortex and striatum depending on validity and delay of reinforcement are analyzed.

It was shown that the two-way interaction between neurons of the frontal cortex and n. accumbens progressively increases, whereas their regularity simultaneously decreases with the rise in impulsiveness and drop in self-control in behavior. In case of the long-latency instrumental reactions, a control of the frontal cortex neurons by neurons of the n. accumbens weakens during presentation of conditioned stimuli only in "impulsive" animals, which is correlated with low network activity of the n. accumbens. Comparison of patterns of fronto-accumbal interactions during performance of the same type of activity revealed similar correlations in the neuronal pairs before and during presentation of conditioned stimuli, whereas different patterns corresponded to different types of activity.

Under conditions of a choice between a high-valuable delayed and a low-valuable immediate food rewards, cats were divided into 3 groups on the basis of their individual strategy of behavior: (1) choosing predominantly the high-valuable reward because of inhibition of the instrumental response (capable of self-control), (2) choosing predominantly the immediate low-valuable reward (impulsive), and (3) with a mixed pattern of reactions (ambivalent). Coherent activity of nucleus accumbens neurons which was a characteristic of interactions between nearby cells was assessed by the method of crosscorrelation. It was found that the total number of interneuronal interactions in cats capable of self-control exceeded that displayed by impulsive cats. In those rare cases when impulsive cats performed long-latency responses not typical of them, the number of interneuronal interactions was the same as during the self-control behavior. In animals of different groups, the number of interneuronal interactions was higher during erroneous responses as compared to correctly performed reactions. The results suggest an important role of systemic activity of neurons in the nucleus accumbens in the organization of the long-latency reaction pattern, characteristic of self-control behavior.

The current review describes the modem Parkinson's disease models in animals, their advantages, limitations and disadvantages. It was noted that the most widespread up-to-date models based on etiology of the Parkinson's disease. Although toxins mostly produce the Parkinson's disease, a study of involved genes allows investigating not only inherited but also sporadic (not inherited) forms of disease since the same genes are involved in both cases. Mutations of genes lead to formation of "mutant" toxic proteins, which produce a death of the specialized neurons of the nigrostriatal dopaminergic system and the development of Parkinson's disease. A significant place in the review takes adescription of characteristics of the toxic models produced by 6-OHDA, MPTP and rotenone, their similarities and differences in pathogenetic mechanisms of the Parkinson's disease development. On the basis of the considered experimental models of Parkinson's disease a conclusion has been done that none of these models may in full and adequate scale imitate the entire clinical, pathophysiological, morphological, biochemical and other aspects of the Parkinson's disease development.

Two experimental models with a choice between two reinforcements were used for assessment of individual typological features of dogs. In the first model dogs were given the choice of homogeneous food reinforcements: between less valuable constantly delivered reinforcement and more valuable reinforcement but delivered with low probabilities. In the second model the dogs had the choice of heterogeneous reinforcements: between performing alimentary and defensive reactions. Under conditions of rise of uncertainty owing to a decrease in probability of getting the valuable food, two dogs continued to prefer the valuable reinforcement, while the third animal gradually shifted its behavior from the choice of a highly valuable but infrequent reward to a less valuable but easily achieved reinforcement. Under condition of choice between the valuable food reinforcement and avoidance of electrocutaneous stimulation, the first two dogs preferred food, whereas the third animal which had been previously oriented to the choice of the low-valuable constant reinforcement, steadily preferred the avoidance behavior. The data obtained are consistent with the hypothesis according to which the individual typological characteristics of animals's (human's) behavior substantially depend on two parameters: extent of environmental uncertainty and subjective features of reinforcement assessment.

In this paper the problem of "impulsive" and "self-control" behaviour in animals and the experimental models for their assessment are discussed. It is pointed out that a widely accepted model for assessment of impulsive behaviour in animals predominantly measures their ongoing properties of impulsivity/self-control independently on belonging them to the certain types of higher nervous activity. In contrary, our model at the first instance assesses the typological characteristics of animals, including impulsivity and self-control, by their abilities to perform or not to perform an appropriate behaviour. The differences in the data obtained by these two different models and the possible reasons for it are discussed.

The influence of two selective antagonists of the dopaminergic receptors, raclopride (D2) and SCH 23 390 (D1) on behavior of "impulsive" and "self-controlled" cats was similar directed. A selective blockade of the dopaminergic D1/D2 receptors by use of raclopride and SCH 23 390 changed a behavioural choice strategy of two different by validity and delay reinforcements in impulsive cats, but did not change it substantially in "self-controlled" animals. Increase of doses of raclopride and SCH 23 390 led to decrease of a part of the short-latency and increase of a part of the long-latency reactions (pedal pressings) in a total number of all effective responses. This occurred only in "impulsive" animals, that indicates probably the decrease of impulsive properties of their behaviour. Both compounds did not affect the choice strategy (a low quality immediate vs. a high quality delayed reinforcements) in "self-control" animals, but elicited more errors and inhibitory responses in their behavior. The data obtained are not consistent with the "dopamine" hypothesis, which predicts increase of impulsivity under influence of dopaminergic antagonists. The reasons that might lead to the data obtained are discussed.

A blockade of the dopaminergic D1/D2 receptors by systemic administration of haloperidol (0.05-0.5 mg/kg) produced a dose-dependent increase in inhibition of conditioned alimentary behavior in cats under conditions of choice between a valuable delayed reward and a less valuable immediate reward. Administration of haloperidol produced a progressive decrease in the number of effective instrumental reactions, but did not affect the choice between short- and long-latency reactions and their mean latencies. The data obtained do not support a hypothesis that the blockade of dopaminergic receptors shifts behavior towards impulsive reactions. The reasons why the results do not support the hypothesis are discussed.

In this paper we have attempted to relate and explain the activity of the brain different integrative levels, which ends up with occurrence of a goal-directed behaviour and reinforcement. Two main mechanisms of responding to subjects and events of external environment, as rapid executive reactions and slow motivational-emotional states, have been marked out. Each mechanism gets its own neurochemical basis, ways of information transmission and molecular-genetic programs for the specialized metabolic reactions. Together both mechanisms form a unique spatial-temporal continuum of neural processes aimed to produce the beneficial activity and reinforce it by subjectively perceived emotional states.

A hypothesis is proposed according to which there is a strong similarity between the individual typological features of animals (humans) and different stages of learning processes. The hypothesis is supported by the results of comparisons of psychophysiological and neurochemical indices of different stages of conditioning and various typologies of higher nervous activity. Such comparisons reveal a high similarity between the generalization phase and impulsivity, the phase a learned conditioned reflex and self-controlled behaviour, and overlearned CR and a state of "psychosis". Functional states close to pathology and possibilities of development and manifestation of several psychotic states depending on psychophysiological and neurochemical organization of learning processes are also considered.

At the first part of the paper a number of conceptions about psychophysiological mechanisms of reinforcement and its role in brain system activity is presented. At the second part, a significance of the mesolimbic and mesocortical dopaminergic systems in reinforcement process and the relationships between different components of behavioural control (signal, memory, actions, etc.) and intensity of dopamine transmission at the level of n. accumbens and frontal cortex are considered. At the final part of the paper the results of development of some psychopathologies and marginal conditions, related to a low or high content of dopamine in the above-mentioned structures, and possible neurophysiological mechanisms of their formation are presented.

A new technically simple and procedurally easy model of discrimination learning in mice has been proposed. The model allows to reach a quick rate of learning; to use the various characteristics of objects (form, color, size, etc) within the same sensory modality as a conditional stimulus; to transfer discrimination from one signal characteristic to the other (for instance from a color to a size); and to assess behaviour in a situation closely approached to conditions of the natural environment.

In this paper some new methods for studying of general cognitive ability, g, and their experimental testing on mice are proposed. Instead of techniques based on learning processes with application of many trials and gradual elaboration of a habit, the proposed methods allow to assess behaviour by using only one or a few trials and to compare such behaviour with conceptual activity.

The paper reviews general cognitive ability (g), the ways of its measurement, and genetic and behavioural aspects of its investigations. The criteria for assessment of cognitive abilities in animals are also suggested and described. Based on these criteria the new behavioural methods and procedures are developed for investigation of general cognitive ability.

This review describes a role of stress in formation of the primary drug-taking behaviour and the effects of stress on a drug-seeking behaviour after withdrawal of drugs. The psychophysiological and neurochemical mechanisms of the rewarding and aversive states during a drug taking and after its withdrawal are considered. A role of separate neurotransmitters and their interactions in formation of drug dependence and the effects of stress on neuroadaptive changes in these neurotransmitter systems are described. A review of the structures involved in mediation of the stress effects and a drug-seeking behaviour is also discussed.

Alimentary and defensive instrumental conditioned responses (CRs) to light flashes, electrical stimulation of the dorsal hippocampus and the nucleus caudatus were elaborated in seven dogs. These CRs were tested by electrostimulation of the limbic structures and the basal ganglia. Motor and vegetative components of CRs were compared. If there occurred an instrumental movement during the conditioned stimulus the heart rate increased with a high probability. If there were no movement the heart rate increase approached the level of significance only in five dogs of seven. The heart rate always increased in the positive generalization tests while in the negative ones the heart rate either decreased or increased to a lesser degree.

In experiments with dogs was shown the role of motivational and emotional structures of the hypothalamus in reproduction of the adaptive motor reaction both in classical and instrumental conditioned reflexes (alimentary and defensive). Change of parameters of electrostimulation gave a possibility to activate differentially the motivational, emotional negative, and emotional positive structures of the hypothalamus. Electrostimulation of the motivational structures reproduced alimentary but not defensive adaptive motor reaction and decreased the threshold of the motor reaction which was used as a signal during classical alimentary conditioning. Electrostimulation of the emotional negative structures reproduced defensive adaptive reaction and inhibited alimentary unconditioned response. Elaboration of the avoidance of the stimulation of the lateral hypothalamus was a proof for the activation of the emotional negative structures. Electrostimulation of the emotional positive structures which was used as an unconditioned stimulus during self-stimulation conditioning reproduced neither defensive nor alimentary conditioned response.

In experiments with dogs was shown that the activating electrostimulation (200 cps; 0.5 ms; 15-20 V) of the emotional positive structures of the hypothalamus (having been able to evoke self-stimulation) reproduced neither defensive nor alimentary adaptive motor reaction. Moreover, such a stimulation inhibited both alimentary (unconditioned and instrumental) and defensive instrumental conditioned responses.

In experiments in dogs it has been found that testing electrical stimulation of the lateral hypothalamus (duration of this stimulation--5-7 s), of the ventromedial hypothalamus and of the substantia grisea centralis of mesencephalon reproduced earlier elaborated acid-defensive instrumental conditioned reflex. This fact takes place due to the activation of the brain structures of negative emotion.

In experiments on 6 dogs it has been shown that in the EPs led from the hippocampus in response to electrostimulation of limbic structures and from the latters at the hippocampus stimulation, initial negativity, after positivity and late negative wave are the most stable components. At transition from one functional state to another two latter waves are subjected to the greatest changes. Amplitude-temporal characteristics of intralimbic EPs depend on the level and type of motivation, degree of emotional stress and properties of conditioned reaction.

In dogs with the electrodes implanted in the hippocampus, amygdala, septum and hypothalamus an instrumental alimentary conditioned reflex (CR) was elaborated to electrostimulation of the hippocampus. Intralimbic evoked potentials (EPs) were studied during the elaboration and extinction of this reflex and during stimulations of limbic structures conducted with the purpose of CR generalization checking. Late EP components in the lateral hypothalamus and central nucleus of the amygdala changed during CR elaboration and extinction and in the hippocampus during amygdala testing. In both cases the amplitude of trace positivity and of slow negative wave was less, when during stimulation of the structure an instrumental movement was initiated than at its absence.

In experiments on two dogs it has been found that testing electric stimulation of the lateral hypothalamus reproduces instrumental movement in case of elaborated alimentary instrumental conditioned reflexes (CR) to a tone and does not reproduce it at elaborated acid-defensive instrumental CR. Under testing electric stimulation of the medial hypothalamus the instrumental movement practically is not reproduced neither in alimentary nor in defensive situation. Appearance of instrumental movement at LH electro-stimulation in alimentary situation is connected with activation of backward conditioned connection from motivation "alimentary" LH centre to representation of this movement in the motor cortex.

In experiments on three dogs there was shown that testing electrostimulation of the lateral hypothalamus reproduced the motor reaction which is a signal stimulus at elaboration of classic alimentary conditioned reflexes (CRs) and did not reproduce it at elaboration of classic defensive CR. Testing electrostimulation of medial parts of the hypothalamus reproduced, as LH electrostimulation the "signal" motor reaction, but in less percentage of cases, during elaboration of classic alimentary CRs and did not reproduce it at elaboration of classic defensive CRs. The reproduction of the signal motor reaction at LH electrostimulation is connected with activation of backward conditioned connection from motivation structures of the hypothalamus to representation of the signal stimulus in the motor cortex.

In dogs with electrodes implanted into the brain, a defensive instrumental conditioned reflex (CR) was elaborated to light flashes, stimulation of the dorsal hippocampus (DH) and caudate nucleus (CN) stimulation. Reproducibility of the learned movement was tested for the contralateral DN, CN, nucleus accumbens (AN) and pallid globe (PG). In the second series the percent of the elicited movements was compared to EPs, appearing in response to signal and testing stimulation. The degree was elucidated of structures participation in motivational, signal and executive links of CR. Low degree of AN participation in the executive CR link (2-nd series) and a high degree of AN and PG participation in the signal link (3-d series) were shown. Thus, intrasystemic CR generalization was more effective than the intersystemic one.

In experiments on 3 dogs it was shown that instrumental defensive conditioned reflex (CR) to electrical stimulation of the hippocampus is generalized within the limbic system (LS). The rate of generalization depended on the place of testing stimuli in LS. Stimulation of the medial parts of LS at the stage of stabilized initial reflex did not produce the generalized CRs, while they appeared distinctly in response to stimulation of the lateral parts of LS. In the process of elaboration of heterogeneous CRs (defensive and alimentary) to electrical stimulation of the hippocampus, generalized conditioned reactions from some brain structures appeared in both situations to the same degree while from other structures--with considerable differences. These data point to a possible participation in the genesis of the generalized CRs both of signal and reinforcing brain mechanisms.

Increased negative discordance of the dominating mode of the pressing duration histogram (PDH), which correlates with the growth of fixed bursts of stimulation is accompanied by a progressive decrease in the reinforcing properties of self-stimulation (SS), avoidance of the pedal and at the same time by a change of behavioral grooming reactions in the intervals between SS for search and consummatory reactions. Hunger considerably shortens the preferable duration of pressing or leads to the appearance of an additional mode on the PDH. With the change of the dominating PDH mode from positive discordance to a negative one, brain stimulation acquires aversive properties which are apparently due to the activation of the mechanisms of specific motivations.

Alimentary instrumental conditioned reflex (CR) was elaborated in dogs to light flashes (I series), electrostimulation (ES) of the hippocampus (II series) and the hypothalamus (III series). Nonreinforced ES of the hypothalamus, amygdala, hippocampus and septum reproduced pressings on the pedal to the least extent in the I series (17-40% of trials), increasing in the II-nd one up to 40-87% during stimulation of the lateral hypothalamus, medial amygdala and contralateral hippocampus. In the III-rd series the number of pressings increased statistically significantly in comparison with the I-st series for most structures. Probably, besides the artificial increase of motivation during ES of the limbic structures which took place in all series, in the II-nd and III-rd series significance for movement reproduction was acquired by CR generalization appearing due to close interconnection of the structures. In this phenomenon connections (evaluated by the EPs) from the tested structures to the initially signal one are important.

In experiments on 9 rats, the study of evoked potentials (EPs) of the CA1 field of the dorsal hippocampus to stimulation of its symmetrical part serving as a signal of drinking conditioned reflex (CR) showed that during reflex elaboration, the amplitude of the main EP components significantly decreased; CR did not appear when the population spike (PS) was absent in the hippocampal response. PS always accompanying CR was not specific only of it, it was also recorded at other behavioural reactions. Changes of fascia dentata EPs in the process of CR elaboration to stimulation of its symmetrical part consisted in decrease of the initial negative wave and increase of the positive one. The obtained data point to a significant reconstruction of excitatory and inhibitory inputs to the hippocampus and fascia dentata under the influence of conditioned activity.

Mono- and polymodal histograms of pauses duration were obtained in rats during self-stimulation (SS) through electrodes implanted in the lateral hypothalamus. Changes in motivational state (deprivation--satiation) did not markedly affect the histogram pattern. It is concluded that the SS drive mechanism is not connected with natural motivations. In all experiments, a high negative correlation between "optimal criterion" parameters and model pause duration is obtained. It is suggested that one and the same mechanism underlies both the SS-reinforcement and drive. Reinforcement is probably connected with current excitation of reinforcing structures during stimulation, whereas the drive is caused by trace activation of the same cerebral structures after the stimulation.

The dependence of self-stimulation frequency on stimulation parameters (current intensity, stimulation frequency, pulse duration, duration of pulse bursts) was studied in fifteen rats with monopolar electrodes implanted in the lateral hypothalamus, using rectangular current pulses for brain stimulation. All the experiments revealed qualitatively similar response surfaces to the combined change of stimulation frequency and pulse duration Self-stimulation frequency is connected in a non-linear way with the "specific charge" per unit of time, and in an approximately linear way, with the duration of the pulse burst. Regression equations are determined which precisely enough described the kind of response surface (R =0.7 to 0.95).

Instrumental defensive conditioned reflex elaborated in dogs to stimulation of the dorsal and ventral hippocampus, also appeared, due to generalization, in response to stimulation of a number of limbic structures. Two types of changes in the generalization effects (estimated by parameters of motor conditioned reaction) were observed in the course of conditioned reflex stabilization: enhancement (in response to stimulation of the lateral hypothalamus, lateral nucleus of septum, limbic cortex) and weakening toward complete disappearance (in response to stimulation of the medial nucleus of amygdala and medial hypothalamus). Manifestation of the generalization phenomenon from the brain structures, which are not involved initially into conditioned activity, suggests the existence of close functional connections between these structures and the hippocampus.

In experiments on thirteen rats with electrodes in the lateral hypothalamus, with a simultaneous change in current intensity I and of stimulation duration T, two variants were obtained of the empirical response surface of the self-stimulation (SS) frequency: with the maximum SS frequency, located within the surface boundaries (peak variant), and with the maximum at one of its boundaries (side variant). An equation has also been deduced on the regression of SS frequency on the parameters I and T, which quite accurately defines the experimental and rated data (R = 0.57 divided by 0.97). It has been established that current intensity has a greater effect on SS frequency as compared with the stimulation duration and that the influences of these parameters are relatively independent of one another.

In experiments on 6 dogs an instrumental defensive conditioned reflex was elaborated to electrical stimulation of the ventral and dorsal hippocampus. This reflex possessed the same characteristics as reflexes to distant stimuli: it became extinguished when the reinforcement was discontinued; it reappeared when the reinforcement was resumed, and it was subject to generalization. In the course of reflex elaboration, the hippocampus function underwent a substantial reorganization. Initially it consisted in inhibition of behavioural reactions; following the reflex elaboration, a general motor activity took place anticipating conditioned paw lift.

To study functional connections in the limbic system (LS), a model was used of instrumental alimentary CR, elaborated in response to low-frequency hippocampus electrostimulation with testing of its generalization within the LS. The dependence was established of the generalization on activation of corresponding pathways between the signal and tested brain structures, the activation of pathways was estimated by EPs recorded in limbic structures in response to hippocampus stimulation (during CR performance), or vice versa (in generalization trials). It turned out that for the appearance of CR generalization, two-way connections between signal and tested brain structures or connections only to the signal structure are more important. One-way connections from the signal structure to tested ones, judging by data, are not important for appearance of the CR generalization in used model of conditioning.